EP1745851B1 - Procede, dispositif et programme pour la classification des liquides - Google Patents

Procede, dispositif et programme pour la classification des liquides Download PDF

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Publication number
EP1745851B1
EP1745851B1 EP06116504.9A EP06116504A EP1745851B1 EP 1745851 B1 EP1745851 B1 EP 1745851B1 EP 06116504 A EP06116504 A EP 06116504A EP 1745851 B1 EP1745851 B1 EP 1745851B1
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EP
European Patent Office
Prior art keywords
pressure
liquid
fluid
pipette tip
chamber
Prior art date
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EP06116504.9A
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German (de)
English (en)
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EP1745851A1 (fr
Inventor
Nikolaus Dr. Ingenhoven
Robert Dr. Liebhard
Adi Zuppiger
Werner Dr. Hälg
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Tecan Trading AG
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Tecan Trading AG
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G01N1/14—Suction devices, e.g. pumps; Ejector devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/146—Employing pressure sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N2035/1025—Fluid level sensing
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/113332—Automated chemical analysis with conveyance of sample along a test line in a container or rack
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/115831—Condition or time responsive
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Definitions

  • the invention relates to a method for selecting pipetting parameters for a liquid in which a fluid space communicates with a measuring space and the internal pressure of this measuring space is monitored by a pressure sensor, and in which at least a first part of this fluid space is brought into fluid communication with a sample of this liquid.
  • Particularly preferred embodiments of the method according to the invention relate to a pipetting device for the liquid handling of liquid samples.
  • the invention thus includes a method of selecting pipetting parameters for liquids in a pipetting device for aspiration and dispensing of volumes of liquid, such as samples of human body fluids.
  • a pipetting device comprises a pipette tip which is connected to a pump.
  • Automated plants usually include a single pipetting device or multiple pipetting devices that are used on liquid containers located on the workstation of a workstation.
  • Such workstations are often capable of performing a wide variety of work on these fluid samples, such as e.g. optical measurements, pipetting, washing, centrifuging, incubating and filtering.
  • One or more robots now operating on Cartesian or polar coordinates, can be used to process samples at such a workstation.
  • Such robots can be liquid containers, such as. e.g. Wear sample tubes or microplates and reposition.
  • Such robots may also be referred to as a so-called “robotic sample processor” (RSP), such as e.g. as a pipetting device for aspirating and dispensing, or used as a dispenser for distributing liquid samples.
  • RSP robottic sample processor
  • e.g. as a pipetting device for aspirating and dispensing or used as a dispenser for distributing liquid samples.
  • a computer e.g. a computer
  • a key advantage of such systems is that large numbers of fluid samples can be automatically processed over long periods of hours and days without the need for a human operator to interfere with the machining process.
  • known pipetting devices comprise a pipette tip, which is connected to a pump. Some of these devices include a fluid space with which a pressure sensor communicates with a pressure sensor across a gas-filled space. This fluid space is defined by the pipette tip, a first line which connects the pipette tip to a pump, and an active part of this pump.
  • Table 1 sets forth the viscosity, vapor pressure and surface tension for some common solvents.
  • the present invention is therefore based on the object to propose an alternative method with which liquid samples can be selected in a simple manner pipetting and the liquid samples can be pipetted as needed.
  • This object is achieved, for example, by proposing a method in which a fluid space communicates with a measuring space and the internal pressure of this measuring space is monitored by a pressure sensor, and in which at least a first part of this fluid space is in fluid communication with a sample of this fluid is brought.
  • the method according to the invention is characterized in that pressure changes are produced in a substantially continuous fluid column arranged in the fluid space, wherein these pressure changes in the measuring chamber pneumatically connected to the fluid column cause corresponding pressure changes which are picked up by the pressure sensor and converted into measuring signals.
  • which measurement signals are processed by a computer and reproduced as a pressure curve, and the course of this pressure curve is compared with the course of known pressure curves.
  • Such a liquid can then be pipetted correctly, ie dispensed or dispensed with a pipette in a certain amount or in a certain volume into a container, eg a well of a microplate.
  • a parameter set is selected for driving the pipetting device to dispense liquid samples. This selection is made manually or automatically by selecting from a library of parameter sets, on the basis of specified tolerance ranges, the parameter set which comes closest to the set requirements.
  • FIG. 1 shows a vertical section through a device or system suitable for carrying out the method according to the invention, according to a first embodiment and according to a first use.
  • This device comprises a fluid space 2, which communicates with a measuring space 3.
  • This connection is here designed as a direct, open passage between the two chambers 2, 3.
  • the internal pressure of the measuring chamber 3 is monitored by a pressure sensor 4, which is connected to a computer 8.
  • the pressure sensor could be connected directly to the fluid space (cf. Fig. 2 ).
  • a first part 5 of the fluid space which here comprises the entire fluid space 2 of a pipette or pipette tip, is here filled with a gas.
  • the pipette tip touches the surface of a liquid 1, which is presented as a sample 6 in a container 13.
  • Such containers may be of any shape and content and are formed, for example, as sample tubes, microplate wells, wells, or petri dishes.
  • FIG. 2 shows a vertical section through a device or system suitable for carrying out the method according to the invention, according to a second embodiment and according to a second use.
  • This device comprises a fluid space 2, which communicates with a measuring space 3.
  • the fluid space 2 also forms the measuring space 3 at the same time.
  • the internal pressure of the measuring space 3 is monitored by a pressure sensor 4, which is connected to a computer 8.
  • the fluid space 2 of a pipette or pipette tip touches the surface of a liquid 1.
  • the fluid column 7, which here is completely formed by a system liquid 11, experiences pressure variations or pressure fluctuations.
  • FIG. 3 shows a vertical section through a device or system suitable for carrying out the method according to the invention, according to a third embodiment and according to a third use.
  • This device comprises a fluid space 2, which communicates with a measuring space 3.
  • This connection is here as a sealingly arranged between the two rooms 2.3, flexible diaphragm 29 is formed.
  • the internal pressure of the measuring chamber 3 is monitored by a pressure sensor 4, which is connected to a computer 8.
  • a first part 5 of the fluid space which here comprises only the rear part of the fluid space 2 of a pipette or pipette tip, is here filled with an air-gap 39 and with system liquid 11.
  • the system liquid 11 can also be omitted here.
  • the first embodiment see. Fig.
  • the air-gap 39 is arranged in the region of the measuring space 3.
  • this is not mandatory because the membrane 29 protects the measuring space 3 from penetrating sample or system liquid.
  • the pipette tip is slightly immersed in the liquid 1 and sample liquid 6 has already been drawn up into the pipette tip.
  • FIG. 4 shows a vertical section through a device or system suitable for carrying out the method according to the invention, according to a third embodiment and according to a fourth use.
  • This device is the same design as in Fig. 3 shown.
  • the entire fluid space 2 of a pipette or pipette tip is here filled in the region of the tip with an air-gap 39 and otherwise with system liquid 11.
  • the membrane 29 protects the measuring space 3 from penetrating system liquid 11.
  • the pipette tip is slightly immersed in the liquid 1.
  • the fluid column 7, which here comprises a gas and system fluid 11 experiences pressure variations or pressure fluctuations.
  • FIG. 5 shows a vertical section through a device or system suitable for carrying out the method according to the invention, according to a preferred third embodiment and according to a fifth use.
  • This device is the same as that in the FIGS. 3 and 4 shown.
  • the entire fluid space 2 of a pipette or pipette tip, here in the region of the tip is already filled with sample liquid 6, which by means of a small air-gap 39 of the system liquid 11 is disconnected.
  • the membrane 29 protects the measuring space 3 from penetrating system liquid 11.
  • the measuring space 3 can be filled with a gas (eg air or N 2 ). If the measuring space is filled with a liquid (eg oil, water), it may additionally comprise a gas bubble which separates the sensor from the liquid.
  • the pipette tip is still slightly immersed in the liquid 1.
  • the fluid column 7, which here comprises a gas and system liquid 11 experiences pressure variations or pressure fluctuations.
  • the pipette is connected to a pump via a line (both not shown).
  • Such pumps may be arbitrarily selected and are designed to dispense larger volumes in the microliter range or in the small volume range from nano to picoliter, depending on the type.
  • the pressure changes described also effect in each case in the measuring chamber 3, which is pneumatically connected to the fluid column 7, pressure changes which are recorded by the pressure sensor 4 and converted into measurement signals.
  • These measurement signals are processed by the computer 8 and used as a pressure curve 9 (cf. Fig. 7 ). The course of this pressure curve 9 can then be compared with the course of known pressure curves.
  • a significant advantage of the present invention is thus that a hitherto unknown sample liquid can be characterized by a one-time test and a simple comparison and its pipetting parameters can be assigned without many individual parameters of this sample liquid having to be determined in a corresponding multiplicity of experiments.
  • FIG. 6 shows a vertical section through a device or system suitable for carrying out the method according to the invention, according to a third embodiment with a piston pump.
  • the embodiment and the use correspond to those associated with Fig. 4 have been described.
  • the fluid column 7, which comprises an air-gap 39 in the region of the pipette tip, is essentially formed by the system fluid 11.
  • first line 19 which is also filled with system liquid
  • the fluid column 7 is extended to the piston 21 of a piston pump 20.
  • This piston pump 20 is used to generate a negative pressure in the fluid space 2 for aspirating and generating an overpressure in the fluid chamber 2 for dispensing liquid samples 6.
  • This piston pump 20 also serves as a pulse unit 17, with which the substantially homogeneous fluid column 7, extending to the air -gap 39 extends, can be vibrated.
  • the membrane 29 protects the measuring space 3 from penetrating system liquid.
  • the pipette tip is currently removed from a sample liquid 6, so that the situation depicted here occurs when the pipette is prepared with system liquid and an air-gap for sample taking.
  • the pressure sensor 4 is used to detect any gas bubbles in the fluid column, which can be detected by characteristic changes in the caused by the pulse unit 17 pressure fluctuations.
  • FIG. 7 shows a pressure curve 9 by the measured pressure values (in volts) against a time axis (in milliseconds) are plotted.
  • the pressure curve 9 shows characteristic pressure changes, which were generated in this case in a filled with water as the system liquid 11 fluid column.
  • the sample liquid 6 was also water that was separated from the system liquid 11 by an air-gap 39 (compare embodiment without membrane 29 according to FIG Fig. 1 but use according to Fig. 3 ).
  • This sudden, one-sided pulse which is delivered to the fluid column, generates a vibration of the fluid column, which are detected as pressure changes in the measuring chamber 3.
  • This sudden, unilaterally counter-directed pulse which is delivered to the fluid column, again generates a vibration of the fluid column, which are also detected as pressure changes in the measuring chamber 3.
  • the respective course of the upper and lower envelopes 37, 38 of the pressure curve 9 is characteristic of water. Aspiration over a period of about two seconds caused a pressure drop of about 0.2V.
  • FIG. 8 shows a vertical section through a pipetting device.
  • This device or system according to the third embodiment suitable for carrying out the method according to the invention comprises a piston pump 20 (cf. Fig. 6 ).
  • This pump is preferably a "CAVRO XP3000 plus Modular Digital Pump” (Tecan Systems Inc., 2450 Zanker Road, San Jose, CA 95138, USA) or a bellows pump, such as, for example US 5,638,986 is known.
  • the piston 21 is driven by the motor M.
  • This device also comprises a per se known, disposable pipette tip 12, which is attached to a tubular pipette containing the fluid column 7.
  • the pipette tip 12 is attached to a holder 12a.
  • the fluid column 7 is formed by a system fluid 11.
  • the fluid space 2 extends from the active part of the pump, ie from the piston 21, via a line 19 designed according to the device requirements, the fluid column 2 and an air-gap 39 to the tip of the pipette tip 12.
  • the whole, removable pipette tip 12 is provided with a Gas (usually air) filled and slightly immersed in a liquid sample 6, which is located in a container 13.
  • the immersion of the pipette tip 12 into the sample liquid 6 caused pressure changes or pressure fluctuations in the fluid column 7.
  • These pressure changes cause pneumatically connected to the fluid column 7 (preferably separated by a flexible membrane 29) measuring space 3 also pressure changes, which are received by the pressure sensor 4 and converted into measurement signals.
  • These measurement signals are processed by the computer 8 and used as a pressure curve 9 (cf. Fig.
  • this device is ready to begin the aspiration process.
  • this device comprises an additional pressure sensor 4 'in the region of the line 19, which connects the pipette with the piston pump 20 as so-called "tubing".
  • This additional pressure sensor 4 ' is preferably also connected to the computer 8 (not shown).
  • Pipette tips include the shown disposable tips of inert plastic material, eg of inexpensive polypropylene. Also steel needles (with or without, for example, with titanium, platinum or Teflonderivaten coated tips) are also usable and are then preferably used as a fixed, non-disposable pipette tips.
  • FIG. 9 shows a partial section through an electronic mechanical variant of an alternative, pump-independent pulse unit 17, with which also pressure changes in the fluid chamber 2 can be generated.
  • the line 19 is guided by a cylinder 40.
  • a piston 41 is arranged with a wedge 43 which is substantially perpendicular to the closed surface of the conduit 19 movable.
  • the wedge 43 is preferably made of soft plastic material and / or has a rounded edge so that the conduit 19 is not damaged. Other shapes may be selected for the wedge 43, such as spheres or bodies with flat or curved surfaces.
  • a preferably solid bottom 44 closes off the cylinder 40 on the side opposite the piston 41. This movement reversibly deforms the line 19, which triggers the said pulse.
  • this pulse unit can be operated independently of the moving of the pipette in an X, Y or Z direction and independently of the operation of the pump 2o.
  • This pulse unit 17 is particularly suitable for detecting gas bubbles in the system fluid 11, which is located in the fluid space 2.
  • a drive for example, serves as a coil 42.
  • the sample liquid 6 (aspiration) was taken in each case after immersion in the liquid 1 by 10 steps with a calculated flow velocity of 180 ⁇ l / sec and for a duration of about 2 seconds.
  • FIG. 10 shows a single characteristic pressure curve 9 "for the sample liquid water.
  • the pressure in the pipette, ie in the fluid chamber 2 and thus in the measuring chamber 3 increases slowly and continuously from the immersion 30, which is attributed to a capillary action of the pipette tip and thus into this penetrating water
  • the pressure first drops by 0.1 V and then oscillates symmetrically to a pressure reduced by about 0.05 V.
  • the pressure At the end of aspiration 51, the pressure first increases by 0.1 V and then oscillates symmetrically to about 0.05 At the onset 33 of the retraction of the pipette tip from the sample liquid, the pressure increases only insignificantly and drops by about the same amount at the end 34 of the retraction of the pipette tip from the sample liquid. It is noticeable that the initially noted, continuous increase in pressure with the same slope between the endpoints of the activities described n continues.
  • FIG. 11 shows three characteristic pressure curves 9,9 ', 9 "for the sample liquid water The high reproducibility of the results is obvious.
  • FIG. 12 shows a single characteristic pressure curve 9 "for a sample liquid with a water / DMSO mixture
  • the ratio of water to dimethyl sulfoxide was 1: 1
  • the pressure in the pipette, ie in the fluid space 2 and thus in the measuring chamber 3 does not increase substantially from the immersion 30.
  • the pressure At the beginning of aspiration 50, the pressure first drops by 0.08 V and then oscillates asymmetrically to a pressure reduced by approx. 0.025 V.
  • the pressure At the end of the aspiration 51, the pressure first increases by 0.1 V and then vibrates asymmetrically to a pressure that is about 0.015 V higher.
  • FIG. 13 shows three characteristic pressure curves 9,9 ', 9 "for the sample liquid with the water / DMSO mixture in the ratio 1: 1
  • the high reproducibility of the results is obvious
  • the biggest variation concerns the time of exchange with the pipette tip.
  • FIG. 14 shows a single characteristic pressure curve 9 "for the sample liquid DMSO
  • the pressure At the beginning of the aspiration 50 the pressure first drops by 0.066 V and oscillates
  • the pressure At the end of the aspiration 51, the pressure first increases by 0.1 V and then oscillates asymmetrically to a pressure which is higher by about 0.02 V.
  • the pressure increases only insignificantly
  • At the end 34 of the retraction of the pipette tip from the sample liquid it drops and falls by approximately the same amount. It is noticeable that the pressure between the end points of the described activities is constant, but mostly falls slightly with a different gradient.
  • FIG. 15 shows three characteristic pressure curves 9,9 ', 9 "for the sample liquid DMSO The high reproducibility of the results is obvious.
  • FIG. 16 shows a single characteristic pressure curve 9 "for a sample liquid with a water / polyethylene glycol mixture (7% PEG in water) .
  • the pressure in the pipette ie in the fluid chamber 2 and thus in the measuring chamber 3, increases the immersion 30 slowly and continuously, which can be attributed to a capillary action of the pipette tip and thus in this penetrating water / PEG mixture.
  • the pressure At the beginning of the aspiration 50, the pressure first drops by 0.11 V and then oscillates extremely asymmetrically to a pressure reduced by approx. 0.037 V.
  • the pressure At the end of the aspiration 51, the pressure first increases by 0.13 V and then again oscillates extremely asymmetrically to a pressure which is about 0.037 V higher.
  • FIG. 17 shows three characteristic pressure curves 9,9 ', 9 "for the sample liquid with the water / PEG mixture (7% PEG in water) . The high reproducibility of the results is obvious.
  • FIG. 18 shows a single characteristic pressure curve 9 "for the sample liquid acetonitrile.
  • the pressure in the pipette, ie in the fluid chamber 2 and thus in the measuring chamber 3 rises rapidly from the immersion 30 by 0.027 V and increases slowly becoming to about 0.04 V increased pressure
  • the pressure At the beginning of aspiration 50 the pressure first drops by 0.09 V and then oscillates almost symmetrically to a pressure that is only about 0.02 V.
  • FIG. 19 shows three characteristic pressure curves 9,9 ', 9 "for the sample liquid acetonitrile The high reproducibility of the results is obvious despite the complex pressure curves.
  • FIG. 20 shows a single characteristic pressure curve 9 "for the sample liquid acetone.
  • the pressure in the pipette, ie in the fluid chamber 2 and thus in the measuring chamber 3 rises from the immersion 30 first fast to 0.03 V and then increases constantly and steeply to a again about
  • the pressure first drops by 0.076 V and then oscillates symmetrically to a pressure about 0.04 V higher in order to immediately rise again constantly and sharply to the value before the start of aspiration 50.
  • FIG. 21 shows three characteristic pressure curves 9,9 ', 9 "for the sample liquid acetone The high reproducibility of the results is evident despite the extremely complex pressure curves at least until reaching point 51. Thereafter, the curve 9 shows a different behavior due to the presence of a Liquid film at the outlet of the pipette tip results after the expulsion from the sample, this film closes the pipette tip so that the high vapor pressure of the sample liquid further increases the pressure in the interior of the pipette.At a certain overpressure, the film bursts and releases In this case, there is almost no sample liquid in the pipette, which means that the pressure does not increase any further, so in this case the pressure drops back to the pipette Starting level.
  • FIG. 22 Figures 23 and 23 show flow changes in the pipette of a pipetting device or pipetting system suitable for carrying out the method according to the invention when aspirating and dispensing a water sample or an air sample.
  • Flow values [ ⁇ ] are shown as a function of time [t]. The flow values were normalized and are not given in absolute numbers. The time values are given in milliseconds.
  • FIG. 24 shows a superposition of the flux variation curves of FIG Fig. 22 "Water” and 23 “air”.
  • the flow curve “air” (thick line) swings faster and also goes faster in a state of equilibrium than the flow curve "water” (thin line).
  • FIG. 25 shows a subtraction representation of the flux variation curves Fig. 22 "Water” minus 23 “air”.
  • the subtraction was chosen here, so that one obtains an impressive difference image of the two curves. This clearly shows that different samples also cause different flow curves. It is up to the individual user whether he directly evaluates the characteristic flow curve of a sample and with a stored flow curve of a known sample, eg by a superposition as in Fig. 24 , wants to compare. Alternatively or in combination with a direct comparison, mathematical operations, such as. eg in Fig. 25 , to be used for comparison purposes.
  • FIG. 26 shows a sectional view through a micro-diaphragm pump for generating a negative pressure in the pipette tip to aspirate a liquid sample and to generate an overpressure in the pipette tip for dispensing a liquid sample, which FIG. 1 out DE 102 38 564 A1 is known.
  • This known from the prior art pipetting device has two micropumps with passive flap valves.
  • This pipetting device has a first and a second micropump 110 a and 110 b, whose operation in FIG DE 102 38 564 A1 is described in detail.
  • Both micropumps each include a piezoelectric actuator 126, which ale a piezoelectric ceramic layer over a large area on a thin membrane 128 arranged is and serve to reduce or enlarge the pump chamber 116. All references in Fig. 26 were of DE 102 38 564 A1 and are described there.
  • the current consumption of this piezoelectric ceramic layer depends on the hydrostatic pressure which generates the liquid to be pipetted in the pipette tip.
  • the capillary effects, the surface tension and the vapor pressure of the liquid to be pipetted also affect the current consumption of the piezoelectric ceramic layer when aspirating or dispensing a liquid sample.
  • the measurement and recording of the course of this current consumption can therefore also be used to characterize a sample liquid.
  • a micropump with active valves could be used for the same purpose, as in DE 102 38 564 A1 in connection with the FIGS. 2 and 3 are disclosed.
  • the pipette tip 134 may be a steel tip or a combination of a tip adapter and a disposable pipette tip mounted thereon.
  • the micropump can (as in DE 102 38 564 A1 disclosed) for conveying gases, such as air, but also used to convey a system liquid; wherein this system liquid is preferably separated from the sample liquid to be pipetted by an air-gap.

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  • Hydrology & Water Resources (AREA)
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Claims (15)

  1. Procédé pour choisir des paramètres de pipetage pour aspirer et distribuer un échantillon liquide (6) avec un système de pipetage, le système de pipetage comprenant :
    (i) un espace fluidique (2) dans lequel est agencée une colonne de fluide (7) essentiellement continue ;
    (ii) une chambre de mesure (3) comprenant un capteur de pression (4), la chambre de mesure (3) étant en liaison pneumatique avec l'espace fluidique (2) ;
    (iii) une pompe (20) raccordée à l'espace fluidique (2), avec un piston (21) pour déplacer la colonne de fluide (7) dans l'espace fluidique (2) et pour créer une dépression ou une surpression dans l'espace fluidique (2) pour aspirer ou distribuer des échantillons liquides (6) ;
    (iv) une pointe de pipette (12) reliée à l'espace fluidique (2) pour absorber ou délivrer des échantillons liquides (6) ; et
    (v) un ordinateur (8) pour traiter des signaux de mesure enregistrés par le capteur de pression (4),
    le procédé étant caractérisé en ce qu'il comprend des étapes suivantes :
    (a) débuter la mesure de la pression dans l'espace fluidique (2) en tant que pression dans la chambre de mesure (3), enregistrer cette pression dans la chambre de mesure (3) avec le capteur de pression (4) et traiter les signaux de mesure du capteur de pression (4) avec l'ordinateur (8) ;
    (b) immerger la pointe de pipette (12) dans un liquide (1) à partir duquel un échantillon liquide (6) doit être extrait ;
    (c) émettre une impulsion unilatérale sur la colonne de fluide (7) dans l'espace fluidique (2) en déplaçant le piston (21) de la pompe (20) du système de pipetage au début de l'aspiration (50) de l'échantillon liquide (6), cette impulsion unilatérale faisant osciller de manière caractéristique pour l'échantillon liquide prélevé (6) la colonne de fluide (7) dans l'espace fluidique (2) par rapport au liquide (1) ;
    (d) enregistrer ce comportement oscillatoire caractéristique de la colonne de fluide (7) avec le capteur de pression (4) en tant qu'oscillations de pression dans la chambre de mesure (3) et traiter les signaux de mesure produits par le capteur de pression (4) et correspondant aux oscillations de pression dans la chambre de mesure (3) avec l'ordinateur (8) ;
    (e) enregistrer l'évolution de la pression dans l'espace fluidique (2) pendant l'aspiration sous la forme de l'évolution de pression dans la chambre de mesure (3) et traiter les signaux de mesure produits par le capteur de pression (4) et correspondant à l'évolution de pression dans la chambre de mesure (3) avec l'ordinateur (8) ;
    (f) reproduire les signaux de mesure enregistrés et traités avec l'ordinateur (8) dans les étapes (a), (d) et (e) en tant que courbe de pression typique (9), laquelle correspondent à la pression dans l'espace fluidique (2) après l'immersion de la pointe de pipette (12), au comportement oscillatoire caractéristique de la colonne de fluide (7) influencé par l'échantillon liquide aspiré (6) et à l'évolution de la pression dans l'espace fluidique (2) pendant l'aspiration ; et
    (g) comparer cette courbe de pression typique (9) d'un échantillon liquide aspiré (6) reproduite à l'étape (f) avec des courbes de pression (9',9") caractéristiques, connues et obtenues de façon appropriée de liquides connus (1).
  2. Procédé selon la revendication 1, caractérisé en ce que la courbe de pression typique (9) présente une évolution qui, à l'état immergé de la pointe de pipette (12) avant l'aspiration, est caractérisée par :
    - une augmentation, ou
    - une constance, ou
    - une augmentation brusque, ou
    - une augmentation brusque et une augmentation de la pression.
  3. Procédé selon la revendication 1 ou 2, caractérisé en ce que la courbe de pression typique (9) présente une évolution qui, à l'état immergé de la pointe de pipette (12) après le début de l'aspiration (50) de l'échantillon liquide (6), est caractérisée par :
    - une oscillation symétrique, ou
    - une oscillation asymétrique.
  4. Procédé selon l'une des revendications 1 à 3, caractérisé en ce que la courbe de pression typique (9) présente une évolution qui, à l'état immergé de la pointe de pipette (12) pendant l'aspiration, est caractérisée par :
    - une augmentation de la pression, ou
    - une constance de la pression, ou
    - une chute de la pression.
  5. Procédé selon l'une des revendications 1 à 4, caractérisé en ce que la chambre de mesure (3) est remplie d'un gaz.
  6. Procédé selon les revendications 1 à 5, caractérisé en ce que la colonne de fluide (7) comprend un gaz (10) et des liquides et est mise en oscillation par un mouvement soudain vis-à-vis du liquide (1).
  7. Procédé selon les revendications 1 à 5, caractérisé en ce que la colonne de fluide (7) est formée d'un gaz (10) est et mise en oscillation par un mouvement soudain vis-à-vis du liquide (1).
  8. Procédé selon les revendications 1 à 5, caractérisé en ce que la colonne de fluide (7) est formée d'un liquide de système (11) qui est mis en oscillation par un mouvement soudain vis-à-vis de l'échantillon liquide (6).
  9. Procédé selon la revendication 8, caractérisé en ce que le liquide de système (11) et l'échantillon liquide (6) sont séparés l'un de l'autre par un air gap.
  10. Procédé selon l'une des revendications 1 à 9, caractérisé en ce que la courbe de pression typique (9) enregistrée est affichée sur un écran (14) ou imprimée et comparée visuellement avec des courbes de pression (9',9") connues affichées sur l'écran (14) ou imprimées (9',9").
  11. Procédé selon l'une des revendications 1 à 9, caractérisé en ce que la courbe de pression typique (9) enregistrée est interprétée à l'aide d'un algorithme et est comparée mathématiquement à des courbes de pression (9',9") connues et interprétées de façon appropriée.
  12. Procédé selon l'une des revendications 10 ou 11, caractérisé en ce que la courbe de pression typique (9) enregistrée est comparée automatiquement à des courbes de pression (9',9") connues et interprétées de façon appropriée et - si l'évolution des oscillations de pression de la courbe de pression typique (9) se situe dans des limites de tolérance déterminées - on choisit des paramètres de pipetage correspondants des liquides connus pour distribuer l'échantillon liquide (6) prélevé.
  13. Procédé selon l'une des revendications 10 ou 11, caractérisé en ce que la courbe de pression typique (9) enregistrée est comparée automatiquement avec des courbes de pression (9',9") connues et interprétées de façon appropriée, et - si l'évolution des oscillations de pression de la courbe de pression typique (9) est en-dehors des limites de tolérance déterminées - on attribue au échantillon liquide (6) prélevé lors de l'aspiration de nouveaux paramètres de pipetage.
  14. Procédé selon l'une des revendications 12 ou 13, caractérisé en ce que les limites de tolérance sont déterminées avant ou après l'enregistrement des oscillations de pression et avant ou après l'établissement de la courbe de pression typique (9).
  15. Procédé selon l'une des revendications 1 à 14, caractérisé en ce que la courbe de pression typique (9) enregistrée est caractérisée à l'aide de l'évolution de courbes enveloppes supérieures et inférieures (37,38).
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Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7477997B2 (en) * 2005-12-19 2009-01-13 Siemens Healthcare Diagnostics Inc. Method for ascertaining interferants in small liquid samples in an automated clinical analyzer
EP2009449A1 (fr) * 2007-06-06 2008-12-31 Hamilton Bonaduz AG Procédé pour le contrôle d'un procédé de pipetage
ATE526085T1 (de) * 2007-06-15 2011-10-15 Hamilton Bonaduz Ag Probenbehandlungsanordnung für eine flüssigkeitsdosiervorrichtung
EP2123359B1 (fr) 2008-05-06 2011-06-08 Hamilton Bonaduz AG Dispositif de pipetage pour l'aspiration et la distribution d'un fluide de dosage
DE112010002270B4 (de) * 2009-01-30 2013-10-17 Hitachi High-Technologies Corporation Automatischer Analysator und Probenbehandlungsvorrichtung
US8717674B2 (en) * 2009-07-10 2014-05-06 Ikonisys, Inc. Custom filtration slide and filtration apparatus and method
US9927449B2 (en) * 2009-10-01 2018-03-27 Hach Lance Gmbh Method of using cuvette package with RFID parameter transponder and cuvettes with 2D bar code, including photometry
JP4919119B2 (ja) * 2010-01-19 2012-04-18 株式会社日立プラントテクノロジー 試薬分注ノズルによる分取・分注方法および試薬分取・分注機構
US20130045498A1 (en) 2010-03-01 2013-02-21 Novozymes A/S Viscosity pressure assay
DE102011002195B4 (de) * 2011-04-20 2020-07-02 Leica Biosystems Nussloch Gmbh Verfahren und Vorrichtung zum Ablösen und/oder Vereinzeln einer histologischen Probe
JP2013076674A (ja) * 2011-09-30 2013-04-25 Fujifilm Corp 分注装置および吸引ノズル位置制御方法
CN102539802B (zh) * 2011-12-30 2013-07-31 北京信息科技大学 微量移液探测方法
CN103245774A (zh) * 2012-02-07 2013-08-14 奥索临床诊断有限公司 使用测定压力确定离心血液中的状况
WO2014058880A1 (fr) * 2012-10-09 2014-04-17 Misono Kunio Dispositifs d'agitation
ITMI20121803A1 (it) * 2012-10-24 2014-04-25 Altergon Sa Metodo e dispositivo di misura e controllo di dosaggio di piccole quantità di fluido per mezzo di ago risonante, ed ago risonante adatto allo scopo
WO2014169012A1 (fr) * 2013-04-11 2014-10-16 Rarecyte, Inc. Dispositif, système et procédé pour sélectionner un analyte cible
EP3086127A4 (fr) * 2013-12-16 2017-08-02 Shimadzu Corporation Dispositif de collecte de liquide et analyseur automatisé disposé avec celui-ci
WO2015141764A1 (fr) * 2014-03-20 2015-09-24 独立行政法人産業技術総合研究所 Dispositif de pipette et système de traitement de liquide
KR101802571B1 (ko) 2014-12-18 2017-11-28 주식회사 엘지화학 용액 공정용 용매 분류 방법 및 이를 이용한 시스템
GB2535140A (en) * 2015-01-09 2016-08-17 Page Brian Pipette tip, pipette, apparatus and kit for light measurement
JP6676300B2 (ja) * 2015-07-28 2020-04-08 ヤマハ発動機株式会社 対象物移動方法及び装置
US10379131B2 (en) 2015-11-18 2019-08-13 Elbit Systems Of America/Kmc Systems, Inc. Systems and methods for detecting a liquid level
AU2017396218A1 (en) * 2017-01-26 2019-07-18 Shimadzu Corporation Method for treating volatile liquid and device for treating liquid
US10859592B2 (en) * 2017-01-31 2020-12-08 Tecan Trading Ag Method of aspirating by pipetting and pipetting apparatus
CN107389507A (zh) * 2017-06-05 2017-11-24 河北晨阳工贸集团有限公司 一种真石漆粘度测试方法
WO2019060716A1 (fr) * 2017-09-25 2019-03-28 Freenome Holdings, Inc. Méthodes et systèmes d'extraction d'échantillon
US20200116546A1 (en) * 2017-09-27 2020-04-16 Hewlett-Packard Development Company, L.P. Correction factors for fluid dispenses
RU2679232C1 (ru) * 2017-12-06 2019-02-06 Федеральное государственное бюджетное учреждение науки Ордена Ленина и Ордена Октябрьской революции Институт геохимии и аналитической химии им. В.И. Вернадского Российской академии наук (ГЕОХИ РАН) Устройство для отбора пленок нефти и нефтепродуктов с поверхности воды
EP3502656B1 (fr) 2017-12-22 2022-09-21 Tecan Trading Ag Appareil de pipetage, système de manipulation de liquides et procédé de commande de pipetage
CN108061590A (zh) * 2018-01-29 2018-05-22 淮阴工学院 气压式吸液探测器
CN108749807B (zh) * 2018-04-01 2020-06-23 上海俊烈汽车科技有限公司 一种高度集成化的压差传感器工作方法
CA3101051A1 (fr) * 2018-06-07 2019-12-12 Amgen Inc. Mesure en ligne de systeme de remplissage
JP7079352B2 (ja) * 2018-07-03 2022-06-01 シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレイテッド ピペット装置の近接感知のために無脈動空気流を生成する小型圧電空気ポンプ
CN109409417A (zh) * 2018-09-29 2019-03-01 深圳市华讯方舟太赫兹科技有限公司 基于热传导的液体识别方法、装置以及存储装置
DE102018125196A1 (de) * 2018-10-11 2020-04-16 Hamilton Bonaduz Ag Vorrichtung und Verfahren zur Qualitätsbestimmung einer impulsartigen Flüssigkeitsdispensation nach dem Air-Displacement-Prinzip
EP4030170B1 (fr) 2018-12-18 2023-03-01 Tecan Trading AG Classification de procédures de manipulation de liquides à l'aide d'un réseau neuronal
JP6837085B2 (ja) * 2019-01-09 2021-03-03 日本電子株式会社 自動分析装置及びプログラム
JP7154192B2 (ja) * 2019-06-27 2022-10-17 京セラ株式会社 ピペット
WO2024024511A1 (fr) * 2022-07-27 2024-02-01 国立大学法人 東京大学 Dispositif de distribution, dispositif de mélange et dispositif d'analyse
EP4386354A1 (fr) 2022-12-14 2024-06-19 Tecan Trading AG Détermination de paramètres physiques d'un liquide avec simulation

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1252173A (fr) * 1984-07-19 1989-04-04 Thomas C. Jessop Appareil et methode de detection de penetration d'un liquide par un contenant utilise pour aspirer et distribuer le liquide
US4794085A (en) 1984-07-19 1988-12-27 Eastman Kodak Company Apparatus and method for detecting liquid penetration by a container used for aspirating and dispensing the liquid
US4675301A (en) 1985-04-01 1987-06-23 Eastman Kodak Company Method for correcting for changes in air pressure above a liquid to be dispensed from a container mounted on a probe
JP2552408B2 (ja) * 1991-10-18 1996-11-13 アロカ株式会社 液体粘性測定装置
DE4225543A1 (de) * 1992-08-01 1994-02-03 Hoffmann Reinhold Edelsteinimitation
US5638986A (en) 1992-11-06 1997-06-17 Fluilogic Systems Oy Method and equipment for dosing small amounts of liquid quantitatively
US5723795A (en) 1995-12-14 1998-03-03 Abbott Laboratories Fluid handler and method of handling a fluid
EP1035503B2 (fr) * 1999-01-23 2010-03-03 X-ident technology GmbH RFID-Transpondeur avec une surface imprimable
US7306672B2 (en) * 2001-04-06 2007-12-11 California Institute Of Technology Microfluidic free interface diffusion techniques
ATE313805T1 (de) * 2001-03-09 2006-01-15 Hamilton Bonaduz Ag Verfahren und vorrichtung zur beurteilung eines flüssigkeitsdosierungsvorgangs
JP3811652B2 (ja) * 2002-03-05 2006-08-23 株式会社日立ハイテクノロジーズ 分注装置及びそれを用いた自動分析装置
DE10238564B4 (de) 2002-08-22 2005-05-04 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Pipettiereinrichtung
JP3903015B2 (ja) * 2003-02-05 2007-04-11 株式会社日立ハイテクノロジーズ 化学分析装置
US7479391B2 (en) 2004-12-10 2009-01-20 Tecan Trading Ag Pipetting apparatus with integrated liquid level and/or gas bubble detection

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JP5064735B2 (ja) 2012-10-31
US20070020763A1 (en) 2007-01-25
US8551788B2 (en) 2013-10-08
CN1920575A (zh) 2007-02-28
JP2007040990A (ja) 2007-02-15
CN1920575B (zh) 2012-10-24
US8357544B2 (en) 2013-01-22
EP1745851A1 (fr) 2007-01-24

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